Reconstructed Ancestral Enzymes Impose a Fitness Cost upon Modern Bacteria Despite Exhibiting Favourable Biochemical Properties

Journal of Molecular Evolution
Joanne K HobbsVickery L Arcus

Abstract

Ancestral sequence reconstruction has been widely used to study historical enzyme evolution, both from biochemical and cellular perspectives. Two properties of reconstructed ancestral proteins/enzymes are commonly reported--high thermostability and high catalytic activity--compared with their contemporaries. Increased protein stability is associated with lower aggregation rates, higher soluble protein abundance and a greater capacity to evolve, and therefore, these proteins could be considered "superior" to their contemporary counterparts. In this study, we investigate the relationship between the favourable in vitro biochemical properties of reconstructed ancestral enzymes and the organismal fitness they confer in vivo. We have previously reconstructed several ancestors of the enzyme LeuB, which is essential for leucine biosynthesis. Our initial fitness experiments revealed that overexpression of ANC4, a reconstructed LeuB that exhibits high stability and activity, was only able to partially rescue the growth of a ΔleuB strain, and that a strain complemented with this enzyme was outcompeted by strains carrying one of its descendants. When we expanded our study to include five reconstructed LeuBs and one contemporary, we found ...Continue Reading

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Citations

Nov 2, 2016·Proceedings of the National Academy of Sciences of the United States of America·Shion A LimSusan Marqusee
Feb 25, 2017·Journal of Molecular Evolution·Betül KacarEric A Gaucher
Sep 16, 2016·Nature Communications·Ryan N RandallEric A Gaucher
Mar 3, 2018·Acta Crystallographica. Section F, Structural Biology Communications·Lisa BuddrusSusan J Crennell
Dec 22, 2020·Briefings in Bioinformatics·Milos MusilDavid Bednar

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